Research treasure trove as entire Icelandic population genetically profiled

A genetics company claims that it can predict the risk of certain deadly diseases in everybody in Iceland, but ethical rules restrict it from informing those in danger.

deCODE genetics says it established the entire DNA sequence of 10,000 individuals in Iceland which, given the demographical make up of the country, allows the company to accurately establish the DNA make-up of most of the 320,000 population.

It is the most comprehensive population-wide measure of sequence variation, offering new opportunities for diagnostic and therapeutic tools.

The results allow deCODE’s team to identify, for example, every person with the BRCA2 gene mutation “at the touch of a button”, which significantly increases the risk of breast cancer, and BRIP1, linked with ovarian cancer.

Don't push the button

That button, though, must remain well hidden, because the vast majority of Icelanders didn’t partake in the study and, given this is deCODE's own predictions, it’s fairly difficult to find an ethical way that would allow the company to ring up people and tell them they may be at risk of disease.

"This risk could basically be nullified by preventative mastectomies and ovariectomies,” argued the chief executive of deCODE, Dr Kari Stefansson, to the BBC.

“It would be criminal not to take advantage of it and I am convinced that my fellow countrymen will begin to use it pretty soon. We could save these people from dying prematurely, but we are not, because we as a society haven’t agreed on that.

“I personally think that not saving people with these mutations is a crime. This is an enormous risk to a large number of people."

The full list of papers have been published in Nature, and Stefansson is adamant that this is "very much more than a molecular national selfie."

There's more

Other discoveries, in what seems a treasure trove of genetic research, include a rare mutation to a gene called ABDB4 that raises the risk of gallstones, and the gene ABCA7 as a risk factor for Alzheimer’s disease.

There were people with a mutation on a gene called MYL4, which causes early-onset atrial fibrillation, while GNAS prevalence gives clues towards increased thyroid-stimulating hormone levels when maternally inherited.

The latter is something that caught the eye of Oxford University’s Dr Luke Jostins, who claims that the discrepancies between maternal and paternal passing down of the gene were unknown previously.

Jostins called the discovery “super-weird” in the New York Times. “If it is real, it is quite the find, the sort of thing that could really inform some new biology,” he said.

Section C shows the geographical distribution of the minor alleles of the risk-conferring variants in MYL4, ABCB4, GNAS and SLC52A2, in 104,220 chip-typed Icelanders. via deCODE

A contained pool

Iceland was only settled around 1,200 years ago, with Scandanavian, Irish and Scottish settlers descending on the island and staying relatively isolated from the rest of the world for a millennium. This resulted in a fairly small gene pool, with many able to trace their family trees back incredibly far.

“This work is a demonstration of the unique power sequencing gives us for learning more about the history of our species and for contributing to new means of diagnosing, treating and preventing disease,” said Stefansson.

“It also shows how a small population such as ours, with the generous participation of the majority of its citizens, can advance science and medicine worldwide.

“We’re contributing to important tools for making more accurate diagnostics for rare diseases; finding new risk factors and potential drug targets for diseases like Alzheimer’s; and even showing how the Y chromosome, a loner in the paired world of our genome, repairs itself as it passes from father to son.

“Other countries are now preparing to undertake their own large-scale sequencing projects, and I would tell them the rewards are great,” Dr Stefansson concluded.